Modulation of CYP1A1 metabolism: From adverse health effects to chemoprevention and therapeutic options

Mescher, Melina; Haarmann‐Stemmann, Thomas

doi:10.1016/j.pharmthera.2018.02.012

Cited by 98 publications

(64 citation statements)

References 232 publications

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“…In addition, the high level of endogenous AhR ligands, such as the tryptophan derivatives in MDA-MB-231 cells [46], may have led to ligand competition. Since CYP gene activation through AhR, particularly CYP1A1, is mediated by the toxicity of TCDD [47], with a partial antagonistic effect, glyceollins can be candidates for the detoxification of TCDD and other AhR-active toxicants. Some natural compounds, such as genistein and resveratrol, have also shown to antagonize the effect of TCDD [48,49].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Glyceollins as Novel Aryl Hydrocarbon Receptor Ligands and Their Role in Cell Migration

Pham

Lecomte

Guével

et al. 2020

IJMS

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Recent studies strongly support the use of the aryl hydrocarbon receptor (AhR) as a therapeutic target in breast cancer. Glyceollins, a group of soybean phytoalexins, are known to exert therapeutic effects in chronic human diseases and also in cancer. To investigate the interaction between glyceollin I (GI), glyceollin II (GII) and AhR, a computational docking analysis, luciferase assays, immunofluorescence and transcriptome analyses were performed with different cancer cell lines. The docking experiments predicted that GI and GII can enter into the AhR binding pocket, but their interactions with the amino acids of the binding site differ, in part, from those interacting with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Both GI and GII were able to weakly and partially activate AhR, with GII being more potent. The results from the transcriptome assays showed that approximately 10% of the genes regulated by TCDD were also modified by both GI and GII, which could have either antagonistic or synergistic effects upon TCDD activation. In addition, we report here, on the basis of phenotype, that GI and GII inhibit the migration of triple-negative (ER-, PgR-, HER2NEU-) MDA-MB-231 breast cancer cells, and that they inhibit the expression of genes which code for important regulators of cell migration and invasion in cancer tissues. In conclusion, GI and GII are AhR ligands that should be further investigated to determine their usefulness in cancer treatments.

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Section: Discussionmentioning

confidence: 99%

Characterization of Glyceollins as Novel Aryl Hydrocarbon Receptor Ligands and Their Role in Cell Migration

Pham

Lecomte

Guével

et al. 2020

IJMS

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“…CYP1A1 was increased in NEVKP at 30minutes post-reperfusion-as reported after a similar ex-vivo perfusion period in lungs. 82 The AHR is a prominent transcriptional regulator of CYP1A1, 60 and is potently activated by gut-derived protein-bound uremic toxins which accumulate in plasma and tissues in AKI and CKD. 62,63,83,84 This activation is linked with the vascular dysfunction and systemic inflammation of CKD.…”

Section: Discussionmentioning

confidence: 99%

“…AHR-independent pathways also regulate CYP1A1 expression 60,[88][89][90] including PPARA. 91 CYP1A1 has well-described roles in drug metabolism and lipid oxidation.…”

Section: Discussionmentioning

confidence: 99%

“…We conducted a targeted metabolomics analysis on urines collected from NEVKP and SCS at each timepoint. Firstly, we examined if the increased expression of CYP1A1 in NEVKP-treated kidneys or alternatively, the inflammatory pathways noted in the SCS-treated kidneys reflected activation of the aryl hydrocarbon receptor (AHR), 60 as may occur secondary to accumulation of gut-derived uremic toxins (including indoxyl sulfate (IS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG) and hippuric acid (HA)) in AKI 58,61 and CKD. 62,63 Secondly, given our hypothesis that PPARs and PPARGC1A represented likely upstream regulators of our NEVKP-related findings, we evaluated metabolites previously linked to the renoprotective effect of PPARGC1A (betaine, choline, carnitine and niacinamide) in IRI.…”

Section: Urine Metabolitesmentioning

confidence: 99%

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Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis

McEvoy

Clotet-Freixas

Tokár

et al. 2020

Preprint

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Normothermic ex-vivo kidney perfusion (NEVKP) results in significantly improved graft function in porcine auto-transplant models of DCD injury compared to static cold storage (SCS); however, the molecular mechanisms underlying these beneficial effects remain unclear. We performed an unbiased proteomics analysis of 28 kidney biopsies obtained at 3 time points from pig kidneys subjected to 30-minutes of warm ischemia, followed by 8 hours of NEVKP or SCS, and auto-transplantation. 70/6593 proteins quantified were differentially expressed between NEVKP and SCS groups (FDR<0.05). Proteins increased in NEVKP mediated key metabolic processes including fatty acid β-oxidation, the TCA-cycle and oxidative phosphorylation. Comparison of our findings with external datasets of ischemia-reperfusion, and other models of kidney injury confirmed that 47 of our proteins represent a common signature of kidney injury reversed or attenuated by NEVKP. We validated key metabolic proteins (ETFB, CPT2) by immunoblotting. Transcription factor databases identified PPARGC1A, PPARA/G/D and RXRA/B as the upstream regulators of our dataset, and we confirmed their increased expression in NEVKP with RT-PCR. The proteome-level changes observed in NEVKP mediate critical metabolic pathways that may explain the improved graft function observed. These effects may be coordinated by PPAR-family transcription factors, and may represent novel therapeutic targets in ischemia-reperfusion injury.

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“…Upon binding of small molecular weight compounds, this complex dissociates and the AHR shuttles in the nucleus, dimerizes with its partner molecule ARNT and induces gene expression (Murray et al, 2014 ). The probably best-examined AHR target genes encode for the xenobiotic-metabolizing monooxygenases cytochrome P450 (CYP) 1A1, CYP1A2, and CYP1B1, which, in most cases, oxidize the invading chemicals to enhance their polarity and facilitate their excretion (Mescher and Haarmann-Stemmann, 2018 ). Importantly, the ligand-driven activation of AHR is frequently accompanied by a stimulation of other cellular signaling pathways, including NF-κB, epidermal growth factor receptor (EGFR) and MAPK signal transduction (Haarmann-Stemmann et al, 2009 ; Puga et al, 2009 ; Tian, 2009 ).…”

mentioning

confidence: 99%

Commentary: Usage of Mitogen-Activated Protein Kinase Small Molecule Inhibitors: More Than Just Inhibition!

2018

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Modulation of CYP1A1 metabolism: From adverse health effects to chemoprevention and therapeutic options

Cited by 98 publications

References 232 publications

Characterization of Glyceollins as Novel Aryl Hydrocarbon Receptor Ligands and Their Role in Cell Migration

Characterization of Glyceollins as Novel Aryl Hydrocarbon Receptor Ligands and Their Role in Cell Migration

Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis

Commentary: Usage of Mitogen-Activated Protein Kinase Small Molecule Inhibitors: More Than Just Inhibition!

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